Fish oil blunts lung function decrements induced by acute exposure to ozone in young healthy adults: A randomized trial.

BACKGROUND: Over one-third of the U.S. population is exposed to unsafe levels of ozone (O3). Dietary supplementation with fish oil (FO) or olive oil (OO) has shown protection against other air pollutants. This study evaluates potential cardiopulmonary benefits of FO or OO supplementation against acute O3 exposure in young healthy adults. METHODS: Forty-three participants (26 ± 4 years old; 47% female) were randomized to receive 3 g/day of FO, 3 g/day OO, or no supplementation (CTL) for 4 weeks prior to undergoing 2-hour exposures to filtered air and 300 ppb O3 with intermittent exercise on two consecutive days. Outcome measurements included spirometry, sputum neutrophil percentage, blood markers of inflammation, tissue injury and coagulation, vascular function, and heart rate variability. The effects of dietary supplementation and O3 on these outcomes were evaluated with linear mixed-effect models. RESULTS: Compared with filtered air, O3 exposure decreased FVC, FEV1, and FEV1/FVC immediately post exposure regardless of supplementation status. Relative to that in the CTL group, the lung function response to O3 exposure in the FO group was blunted, as evidenced by O3-induced decreases in FEV1 (Normalized CTL -0.40 ± 0.34 L, Normalized FO -0.21 ± 0.27 L) and FEV1/FVC (Normalized CTL -4.67 ± 5.0 %, Normalized FO -1.4 ± 3.18 %) values that were on average 48% and 70% smaller, respectively. Inflammatory responses measured in the sputum immediately post O3 exposure were not different among the three supplementation groups. Systolic blood pressure elevations 20-h post O3 exposure were blunted by OO supplementation. CONCLUSION: FO supplementation appears to offer protective effects against lung function decrements caused by acute O3 exposure in healthy adults.

Systemic inflammatory response to inhaled endotoxin does not correlate with airway response.

BACKGROUND: Endotoxin is a component of particulate matter linked to respiratory disease. Our group has shown that experimental endotoxin inhalation challenge reproducibly triggers neutrophilic inflammation in the airways and in peripheral blood. Sputum induction is currently the only available method for assessing airway neutrophilia but is laborious and time-consuming. This analysis examined the correlation between systemic and airway inflammatory responses to endotoxin to determine if peripheral blood could serve as a surrogate marker for neutrophilic airway inflammation. METHODS: We conducted a retrospective study of 124 inhaled endotoxin challenges conducted at our center using 20,000 endotoxin units (EU) of Clinical Center Reference Endotoxin (CCRE). Venipuncture and induced sputum samples were obtained at baseline and 6 hours after completion of endotoxin challenge. The relationship between change in sputum neutrophils (post-challenge - baseline) and change in peripheral blood neutrophils (post-challenge - baseline) was assessed using Spearman's correlation analyses. RESULTS: Inhaled endotoxin induced a significant increase in mean sputum percent neutrophils and peripheral blood absolute neutrophil counts in healthy adults with or without mild asthma, but no significant correlation was found between airway and systemic neutrophilia (r = 0.13, p = 0.18). Stratification by degree of airway neutrophil response and by atopic or asthmatic status did not change the results. CONCLUSIONS: Inhalation challenge with endotoxin safely and effectively induces airway neutrophilic inflammation in most individuals. Increases in endotoxin-induced peripheral blood neutrophils do not correlate well with airway responses and should not be used as a surrogate marker of airway inflammation.

Vitamin E, γ-tocopherol, reduces airway neutrophil recruitment after inhaled endotoxin challenge in rats and in healthy volunteers.

Epidemiologic studies suggest that dietary vitamin E is an important candidate intervention for asthma. Our group has shown that daily consumption of vitamin E (γ-tocopherol, γT) has anti-inflammatory actions in both rodent and human phase I studies. The objective of this study was to test whether γT supplementation could mitigate a model of neutrophilic airway inflammation in rats and in healthy human volunteers. F344/N rats were randomized to oral gavage with γT versus placebo, followed by intranasal LPS (20µg) challenge. Bronchoalveolar lavage fluid and lung histology were used to assess airway neutrophil recruitment. In a phase IIa clinical study, 13 nonasthmatic subjects completed a double-blinded, placebo-controlled crossover study in which they consumed either a γT-enriched capsule or a sunflower oil placebo capsule. After 7 days of daily supplementation, they underwent an inhaled LPS challenge. Induced sputum was assessed for neutrophils 6 h after inhaled LPS. The effect of γT compared to placebo on airway neutrophils post-LPS was compared using a repeated-measures analysis of variance. In rats, oral γT supplementation significantly reduced tissue infiltration (p<0.05) and accumulation of airway neutrophils (p<0.05) that are elicited by intranasal LPS challenge compared to control rats. In human volunteers, γT treatment significantly decreased induced sputum neutrophils (p=0.03) compared to placebo. Oral supplementation with γT reduced airway neutrophil recruitment in both rat and human models of inhaled LPS challenge. These results suggest that γT is a potential therapeutic candidate for prevention or treatment of neutrophilic airway inflammation in diseased populations.